6beta-thiocyanato pregnane derivatives



United States Patent "cc 3,300,519 1 p Y 6,8-THIOCYANATO PREGNANE DERIVATIVES Taichiro Komeno, Osaka, Japan, assignor to Shionogi & Co., Ltd., Osaka, Japan No Drawing. Filed Dec. 30, 1963, Ser. No. 334,631 Claims priority, application Japan, Jan. 9, 1963,

1- Claim. or. 260-3974) The present invention relates to 6fi-thiocyanato-4-pregnene-3,20-dione and an intermediate therefor.

The said 6,8-thiocyanato-4-pregnene-3,20-dione is represented by the formula:

It is useful as an artificial hormonic substance, i.e. a progestational agent.

The objective 6 8-thiocyanato-4-pregnene-3,20-dione can be prepared from a known steroid, i.e. 3,3,20,20-bisethylenedioxy-a,6a-epoxypregnane [Bowers et al.: Tetrahedron, vol. 7, p. 138 (1959)] according to the following scheme:

SON (I) The starting 3,3,20,20 bisethylenedioxy 5a,6a-epoxypregnane (II) is first subjected to fission of the epoxy linkage. The fission may be accomplished by treating the starting steroid (II) with thiocyanic acid, prepared from potassium thiocyanate and phosphoric acid, in an inert organic solvent (e.g. ether, chloroform, dichloromethane) at room temperature (i.e. to C.).

The resulting product, i.e. 5a-hydroxy-6fi-thiocyanatopregnane-3,20-dione (III), is then subjected to dehydration. The dehydration may be carried out by treating the inter-mediate (III) with thionyl chloride in the presence 3"3 005 Patented Jan. 24, 1961 of an organic base (e.g. pyridine, picoline, triethylamine: while cooling with ice.

The thus produced 6B-thiocyanato-4-pregnene-3 ,20-di one is useful as a progestational agent. For instance when administered to immature female rabbits at a dos of 20 milligrams, it produced statistically significant in crease of uterine weight.

The following examples set forth illustratively pres ently-preferred embodiments of the present invention.

To a solution of potassium thiocyanate (30 g.) in wate (20 ml.), there are added ether (120 ml.) andphosphorit acid (50 g.) whereby the produced thiocyanic acid is re tained in the ether layer. The ether layer is separated ant dried over anhydrous sodium sulfate and then calciun chloride. A solution of 3,3,20,20-bisethylenedioxy-5u,6a epoxypregnane (4.63 g.) in chloroform (40 ml.) is adder thereto, and the resultant mixture is allowed to stand a room temperature (15 to 30 C.) for 48 hours. Th reaction mixture is washed with dilute sodium carbonat solution and water in order, dried and the solvent evapo rated. The residue is dissolved in acetic acid (10( ml.) and heated on a water bath for 30 minutes. Watei is added to the resultant mixture. The precipitated crys tals are collected by filtration, washed with water, drier and recrystallized from a mixture of chloroform ant methanol to give a Sa-hydroxy-6 8-thiocyanatopregnane-3 20-dione (3.93 g.) as crystals melting at 213 to 215 C (decomp.). [a] 58.5:2 (0:1.018 in chloro form).

IR; 1153 3302, 2146, 1720, 1689 emf.

Analysis.Calcd. for C H O NS: C, 67.83; H, 8.02 N, 3.60; S, 8,23. Found: C, 68.14; H, 8.11; N, 3.70; S 8.02.

Example 2 CH3 $19k 0:0 0:0

SCN

3 4 crystallized from a mixture of acetone and hexane to give What is claimed is: 6fl-thiocyanato-4-pregnene-3,20-dione (858- mg.) as erys- 5a-hydr0xy-Gfl-thiocyanatopregnane-S,20-dione.

tals melting at 165 to 167 C. [u] +125.6i2

(-c:1.013 in chloroform). References Cited by the Examiner Tori, et al., Chemistry aiid Industry, September 1963,

IR: 110E013 2166, 1700, 1680, 1612 cmf max. page 1527 relied on.

Arzaly.sis.--Calcd. for C22H29O2NS: C, 71.12; H 7.87; N, 3.77; s, 8.63. Found: c, 71.29; H, 7.98; N, 3:76; 5, LEWIS GOTTS 8.73. E. L. ROBERTS, Examiner. 

